In rabbits bearing the
prostaglandin-producing VX2
carcinoma, the plasma concentration of
13,14-dihydro-15-keto-PGE2 (PGE2-M) was elevated within one week after
tumor implantation and preceded the development of
hypercalcemia. Both the rate of rise and magnitude of the increase were greater for the metabolite than for
PGE2; at the time of peak hyercalcemia (about 4 to 5 weeks after
tumor implantation), the increase over basal in plasma
PGE2-M was about 75 fold whereas it was previously shown that the increase in
PGE2 was less than 2 fold.
Indomethacin, which inhibits
PGE2 synthesis in VX2 cells in culture, lowered in parallel plasma calcaium and
PGE2-M in
tumor-bearing rabbits. Administration of
hydrocortisone to rabbits bearing the VX2
tumor prevented the development of
hypercalcemia when given at the time of
tumor implantation and reversed the elevated plasma
calcium in previously untreated animals; the
steroid hormone also lowered plasma concentrations of
PGE2-M. These findings are consistent with our hypothesis that the hypercalcemic syndrome in VX2
tumor-bearing rabbits is due to the secretion of
PGE2 by the
tumor.